Biotin, vitamin H, is a natural product found largely in the kidney, liver, egg yolk, milk and yeast. The compound is used to prevent symptoms of egg-white injury in experimental animals. Its prime medical use is in various dermatitides.
Biotin has been prepared synthetically by Harris et al. (Science, 97, 447 (1943) and Baker et al. (J. Org. Chem. 12, 167 (1947), among others. None of these syntheses, however, were commercially feasible. The first commercial synthesis of biotin resulted from the work of Goldberg and Stembach (U.S. Pat. Nos. 2,489,235 and 2,489,236).
Many previous biotin syntheses suffer from the disadvantage that stereoisomeric mixtures of intermediates leading to biotin stereoisomers are formed, thus requiring costly and time consuming separations. These separations also lead to decreased yields of biotin. In the instant invention an inexpensiVe and readily available starting material, i.e., a 3-halocycloheptane, preferably 3-bromocycloheptene, is converted to biotin in a stereospecific synthesis, resulting in the obtention of biotin devoid of biologically inactive stereoisomers.
According to the instant invention, biotin is obtained from a relatively inexpensive starting material, in a stereospecific fashion thus avoiding the costly and inefficient chemical separations heretofore required.